Study questions using mice in medical tests

For decades, mice have been the species of choice in the study of human diseases. But now, researchers report stunning evidence that the mouse model has been misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.

The study does not mean that mice are useless models for all human diseases. But, its authors said, it does raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.

“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.

The paper, published in the Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, have a disease that looks like sepsis in humans but is very different.

Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating disorder. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills a quarter to half of them and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.

“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.

“It’s amazing,” Dr. Richard Wenzel, chairman of the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine, said of the new study. “They are absolutely right on.”

Potentially deadly immune responses occur when a person’s immune system responds to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.

The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, often dying.

The group had tried to publish its findings in several papers. One objection, Davis said, was that the researchers had not shown the same gene response had happened in mice.

“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”

“That started us thinking,” he continued. “Is it the same in the mouse or not?” The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.

“We were kind of blown away,” Davis said.

Last modified: March 18, 2013
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